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© 2003 Memorial Sloar-Kettering Cancer Center
(Monograph)
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Full Text |
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Barrie Cassileth
and K. Simon Yeung
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Coriolus
Versicolor
(Coriolus
versicolor, Trametes versicolor, Polyporus versicolor)
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| Clinical Summary |
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Water
extract of the fruiting body and mycelium of the mushroom. Patients use Coriolus
versicolor or its constituents polysaccharide-K (PSK) and
polysaccharide-P (PSP) to stimulate the immune system, reduce chemotherapy
toxicity, and increase the effectiveness of chemotherapy or radiotherapy
for cancer. The beta-glucans PSK and PSP show antiproliferative activity
in animal models and immunostimulant activity in both animal and human
studies. PSK extracts are available for clinical use in Japan. Toxicity is
low; only darkening of the fingernails is reported. When used in
conjunction with chemotherapy, PSK appears to improve survival rates in
gastric and colorectal cancer patients after surgery. Outcomes in breast
cancer, HCC, and leukemia are less impressive. No clinical trials
evaluating PSP are published in the peer-reviewed literature.
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| Scientific Name |
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Coriolus
versicolor, Trametes versicolor, Polyporus versicolor
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| Also Known As |
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PSK,
PSP, Trametes versicolor
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| Brand Name |
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Krestin
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| Purported Uses |
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• Cancer
prevention
• Cancer
treatment
• Chemotherapy
side effects
• Hepatitis
• Herpes
• Immunostimulation
• Infections
• Radiationtherapy
side effects
• Strength
and stamina
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Constituents
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Proteoglycans:
Polysaccharide-K (PSK), a beta-1,4-glucan (isolated from the CM-101 strain),
polysaccharide-P (PSP), isolated from the COV-1 strain.
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| Mechanism Of Action [1], [2], [3], [4] |
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Coriolus
versicolor is thought to be a biological response modifier. The
proteoglycan constituents (PSK and PSP, discussed below) are thought
responsible for its immunostimulant and anti-cancer activities. Whole
extracts of the mushroom may have chemopreventive effects, as inhibition
of 8-OH-dG and superoxide anion formation is seen in vitro.
PSK is thought to enhance both humoral and cellular
immunity. It inhibits tumor growth in vitro and in several allogeneic and
syngeneic tumor models in mice and rats. Animal models show additive
effects and prevention of side effects when PSK is given with
chemotherapeutic agents, including 5-FU, doxorubicin, cyclophosphamide,
tegafur, cisplatin, and mitomycin-C (MMC). Recovery of depressed
humoral immunity is observed when PSK is combined with radiotherapy in
mice. Animal studies support that PSK induces T killer cell activity and
restores depressed immune parameters while inhibiting immunosuppressive
substances. In vitro, PSK induces cytokine expression in human
peripheral blood mononuclear cells. TNF-alpha and IL-8 gene expression are
significantly induced after PSK administration in healthy volunteers and
gastric cancer patients, although individual response varies. In a number
of animal models, oral PSK increases survival and/or suppresses the
formation and metastasis of carcinogen- or radiation-induced tumors. PSK
also inhibits post-surgical growth of recurrent or metastatic tumor cells
in animal models, possibly through inhibition of tumor cell migration,
intravasation, attachment to endothelial cells, and growth. Several animal
studies report of synergism between PSK and biologic therapies, including
a concanavalin A-bound L1210 vaccine and the IgG2a monoclonal antibody
against human colon cancer cells.
PSP induces cytokine production and T-cell proliferation and
prevents cyclophosphamide immune depression in animal models. Peritoneal
macrophages isolated from mice fed PSP show increased production of
reactive nitrogen intermediates, superoxide anions, and tumor necrosis
factor. No in vitro cytotoxicity is seen, but PSP inhibits proliferation
of several tumor cell lines and enhances the effects of radiation against
rat glioma cells in vitro and in vivo. In animal studies, oral
administration inhibits growth of lung adenocarcinoma; intraperitoneal
administration inhibits LLC and sarcoma 180 growth. A small trial of
breast cancer patients treated with PSP shows maintenance of peripheral
white blood counts and platelet counts after three cycles of chemotherapy. In
vitro, PSP inhibits the interaction between HIV-1 gp120 and CD4 receptor,
HIV-1 transcriptase activity, and glycohydrolase enzyme activity
associated with viral glycosylation, but no clinical trials support its
use as an anti-viral agent in vivo. PSP also shows analgesic activity in
mouse models.
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Pharmacokinetics
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Absorption
Animal studies with radiolabeled PSK show that it is partially decomposed
to small molecular products in the digestive tract. The full molecular
spectrum of labeled PSK is absorbed within 24 hours following oral
administration in mice. Peak plasma levels of low molecular weight
substances occur at 0.5-1 h in rats and 1-2 h in rabbits, while molecules
the size of PSK appear in serum after 4, 10, and 24 h.
Distribution
Radiolabeled PSK or its metabolites are detected in the digestive tract,
bone marrow, salivary glands, thymus, adrenal gland, brain, liver, spleen,
pancreas, and tumor tissue in sarcoma-bearing mice. Activity remains high
longest in the liver and bone marrow.
Excretion
Approximately 70% of radiolabeled PSK is excreted in expired air, 20% in
feces, 10% in urine, and 0.8% in bile. Approximately 86% is
excreted within 24 h.
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| Adverse Reactions |
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Infrequent:
Darkening of the fingernails, coughing during administration of powder
drug.
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Drug Interactions
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Acetaminophen:
Theoretically, coriolus versicolor may protect against
acetaminophen-induced liver injury.
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| Lab Interactions |
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None
known
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| Literature Summary And Critique |
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Niimoto
M, et al. Postoperative adjuvant immunochemotherapy with mitomycin C,
futraful, and PSK for gastric cancer. An analysis of data on 579 patients
followed for five years. Jpn J Surg 1988;18:681-6.
A randomized, controlled trial of adjuvant chemotherapy with or without
PSK in 579 patients after curative gastrectomy. Mitomycin C 20mg was
administered on the day of surgery, plus an additional 10mg the following
day for special cases. 1-2 weeks postsurgery, Group A received 3 g PSK,
Group B 600-800 mg futraful (FT), and Group C both PSK and FT for one
year. Patient characteristics were comparable between groups, but were not
noted. 5 year survival rates were 64.1% for Group A, 58.5% for Group B,
and 71.7% in Group C. The difference between Groups B and C was
significant (p<0.01), but not between A and C. This suggests that
PSK enhances the effects of adjuvant chemotherapy after gastrectomy.
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Nakazato
H, et al. Efficacy of immunochemotherapy as adjuvant treatment after curative
resection of gastric cancer. Lancet 1994;343:1122-6.
A randomized, controlled, multicenter evaluation of chemotherapy with or
without PSK in 262 patients after curative gastrectomy. Chemotherapy
consisted of intravenous mitomycin C on postoperative days 1 and 7 plus
150 mg/d oral fluorouracil. The PSK group received 3 g/d oral PSK for 4
weeks alternating with 4 weeks fluorouracil, while control patients
received only fluorouracil alternated with 4 weeks without treatment. Ten
courses were given to both groups. PSK patients experienced a greater
5-year disease-free rate (70.7% vs. 59.4%) and 5-year survival rate (73%
vs 60%) than the control group. Because eligibility criteria included a
positive PPD, this trial only represents the benefits of PSK in patients
with a preserved immune response.
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Mitomi
T, et al. Randomized,
controlled study on adjuvant immunochemotherapy with PSK in curatively
resected colorectal cancer. The Cooperative Study Group of Surgical
Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa). Dis Colon Rectum
1992;35:123-30.
A multicenter trial of mitomycin C (MMC) and 5-flurouracil (5-FU) with or
without PSK in 448 patients with curatively resected colon cancer.
Patients received 6 mg/m2 MMC on the day of and day after surgery and 200
mg/day oral 5-FU for six months either with (n=221) or without (n=227) 3
g/day oral PSK for over 3 years. Demographics and clinical characteristics
were similar between groups, except that PSK patients had significantly
larger rectal tumors than controls. Patients were followed for 3-5 years.
Both disease-free and overall survival curve were significantly better for
patients receiving PSK (p=0.013): Three-year survival estimate for PSK
patients was 85.8%, compared to 79.2% for controls.
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Torisu
M, et al. Significant
prolongation of disease-free period gained by oral polysaccharide K (PSK)
administration after curative surgical operation of colorectal cancer. Cancer
Immunol Immunother 1990;31:261-8.
A randomized, double blind evaluation of PSK (n=56) versus placebo (n=55)
in patients after curative surgery of colorectal cancer. Starting 10-15
days after surgery, patients received 3 g/day PSK or placebo for 2 months,
then 2 g/day until 24 months and 1 g/day thereafter. Clinical
characteristics were similar between groups, although tumor size was not
addressed. Overall and disease free survival were significantly higher in
the PSK group compared to placebo (p<0.05, both). Polymorphonuclear
monocytes from patients receiving PSK showed increased phagocytic and
locomotive activity. Other measured immune parameters, such as skin
reactivity, lymphocyte counts, and immunoglobulin levels, did not differ
significantly between groups. Survival and disease-free survival rates
were generally worse than in other trials combining PSK and
chemotherapeutic agents, indicating that PSK alone is not as effective
after curative surgery of colorectal cancer.
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Iino
Y, et al. Immunochemotherapies
versus chemotherapy as adjuvant treatment after curative resection of
operable breast cancer. Anticancer Res 1995;15:2907-11.
A
randomized evaluation of combination chemotherapy (5-fluorouracil,
cyclophosphamide, mitomycin C, and predonisolone – FEMP) with 3 g/d PSK
or 150 mg/d levamisole (LMS) in 227 patients with operable breast cancer
with vascular invasion in the tumor and/or in the metastatic lymph node.
Each treatment, FEMP, FEMP+LMS, or FEMP+PSK, lasted 28 days and was
carried out at 6-month intervals for 5 years. Patients receiving FEMP+PSK
had a slightly better survival curve than the FEMP group (p=0.0706),
although differences in survival (OS) and disease-free survival (DFS) were
not significant between the 3 groups. Ten-year DFS rates were 64.6% in the
FEMP, 70.7% in the FEMP+LMS, and 74.1% in the FEMP+PSK group.
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Ohno
R, et al. A
randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in
adults using a protein-bound polysaccharide preparation. Cancer Immunol
Immunother 1984;18:149-54.
A
randomized controlled trial of maintenance chemotherapy with (n=36) or
without (n=31) PSK in 17 patients with acute nonlymphocytic leukemia (ANLL)
who had achieved complete remission and had received consolidation
therapy. Maintenance chemotherapy consisted of 2 regimens ((1) DCMP or
BHAC-MP and (2) vincristine, cyclophosphamide, 6-mercaptopurine, and
prednisolone) given alternately every 5th week for 2 years. 3
g/d PSK was given every day indefinitely except during maintenance
chemotherapy. Remission duration and survival length analyzed 6 months
after the last entry showed borderline beneficial effect of PSK (p=0.089),
but analysis at 24 months showed no significant difference.
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Suto
T, et al. Clinical
study of biological response modifiers as maintenance therapy for
hepatocellular carcinoma. Cancer Chemother Pharmacol 1994;33:145-8.
A
randomized controlled trial comparing 100-150 mg 5-FU with or without PSK,
lentinan, or OK-432 as a maintenance therapy for HCC after treatment with
percutaneous ethanol injection (PEI), transcatheter arterial embolization
(TAE), or arterial infusion of antitumor agents (AI). All patients
received 100-150 mg/d 5-FU. Group I (n=15) was given 3 g/d oral PSK for 7
days every 2 weeks; Group II (n=15) received intravenous injection of 2 mg
lentinan once a week; Group III (n=12) OK-432 once a week; and Group IV
(n=16) received 5-FU only. Patient characteristics were comparable except
that Group I patients tended to have worse reserve liver function and PEI
was performed more often in Group IV. Mean survival time did not differ
significantly between groups.
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| References |
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[1] Kim
HS, Kacew S, Lee BM. In vitro chemopreventive effects of plant
polysaccharides (Aloe barbadensis Miller, Lentinus edodes, Ganoderma
lucidum and Coriolus versicolor). Carcinogenesis 1999;23:1637-40.
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[2] Kato
M, Hirose K, Hakozaki M, et al. Induction of gene expression for
immunomodulating cytokines in peripheral blood mononuclear cells in
response to orally administered PSK , an immunomodulating protein-bound
polysaccharide. Cancer Immunol Immunother 1995;40:152-6.
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[3] Kobayashi H, Matsunaga K, Fujii M. PSK as a chemopreventive agent. Cancer
Epidemiol Biomarkers Prev 1993;2:271-6.
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[4] Tsukagoshi
S, et al. Krestin (PSK). Cancer Treat Rev 1984;11:131-55.
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[5]
Kobayashi H, Matsunaga K, Oguchi Y. Antimetastatic effects of PSK (Krestin),
a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer
Epidemiol Biomarkers Prev 1995;4:275-81.
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[6]
Nakazato
H, et al. Efficacy of immunochemotherapy as adjuvant treatment after curative
resection of gastric cancer. Lancet 1994;343:1122-6.
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[7]
Kanoh
T, Saito K, Matsunaga K, Oguchi Y, Taniguchi N, Endoh H, Yoshimura M,
Fujii T, Yoshikumi C. Enhancement of the antitumor effect by the
concurrent use of a monoclonal antibody and the protein-bound
polysaccharide PSK in mice bearing a human cancer cell line. In
Vivo 1994;8:241-5.
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[8]
Ng
TB. A review of
research on the protein-bound polysaccharide (polysaccharopeptide, PSP)
from the mushroom Coriolus versicolor (Basidomycetes: polyporacae). Gen
Pharmac 1998;30:1-4.
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[9]
Liu
WK, et al. Activation
of peritoneal macrophages by polysaccharopeptide from the mushroom,
Coriolus versicolor. Immunopharmacology 1993;26:139-46.
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[10]
Mao
XW. Evaluation of polysaccharopeptide effects against C6 glioma in
combination with radiation. Oncology
2001;61:243-53.
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[11]
Dong
Y, et al. Antitumor
effects of a refined polysaccharide peptide fraction isolated from
Coriolus versicolor: in vitro and in vivo studies. Res
Commun Mol Pathol Pharmacol 1996;92:140-8.
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[12]
Shiu WCT, Leung TWT, Tao M. A clinical study of PSP on peripheral blood
counts during chemotherapy. Phytother Res 1992;6:217-8.
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[13]
Ng
TB, Chan WY. Polysaccharopeptide from the mushroom Coriolus versicolor
possesses analgesic acitivity but does not produce adverse effects on
female reproductive or embryonic development in mice. Gen Pharmac 1997;29:269-73.
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[14]
Kidd
PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern
Med Rev 2000;5:4-27.
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[15]
Ikuzawa
M, et al. Fate
and distribution of an antitumor protein-bound polysaccharide PSK (Krestin).
Int J
Immunopharmacol 1988;10:415-23. |
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| Written |
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08/17/2002 |
| Updated |
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11/25/2002
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Disclaimer: http://www.mskcc.org/mskcc/print/11790.cfm |
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Source:
http://www.mskcc.org/mskcc/print/11571.cfm?RecordID=530 |
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